Raltegravir potassium is chemically known as potassium N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide. Raltegravir potassium is a potent HL1 integrase inhibitor which is used for treatment of HL1 infections, AIDS, and Aids Related Complex (ARC).

Raltegravir disclosed in U.S. Pat. No. 7,169,780 B2 and potassium salt of Raltegravir is specifically described by U.S. Pat. No. 7,754,731 B2. Raltegravir exhibits poor aqueous solubility whereas the potassium salt of Raltegravir is significantly more soluble in water and exhibit improved pharmacokinetics in animal models over Raltegravir free acid.
Polymorphism is the ability of a compound to exist in two or more different crystalline phases that differ in arrangement of the molecules in crystal lattice. Although polymorphs have the same chemical composition, they differ in packing and geometrical arrangement and exhibit different physical properties such as melting point, density, stability, and solubility.
Extensive study is carried out in pharmaceutical industry for development of different polymorphs of various drug substances, to obtain suitable polymorphs that possess improved performance characteristics such as aqueous solubility, improved bioavailability, chemical stability, shelf life etc.
Raltegravir potassium can exist in different polymorphic forms, which differ from each other in terms of stability, physical properties and pharmacokinetics.
The PCT application WO 2006060712 A2 discloses two anhydrous crystalline forms of Raltegravir potassium viz., Form 1 and Form 3 and one crystalline hydrate designated as Form 2.
The PCT application WO 2011024192 A2 discloses the preparation of Raltegravir potassium amorphous form and crystalline forms 1, 2 and 3.
The PCT application WO 2017001996 A1 and Indian Publication Nos. 3346/DEL/2012, 5282/CHE/2013 discloses the preparation of Raltegravir potassium Form 3.
However, the known processes for preparation of the crystalline Raltegravir potassium Form 3 suffer from several disadvantages such as lack of reproducibility; contamination of other solid state forms; require the use of column chromatographic purifications; the use of excess amounts of solvents which generate a large quantity of chemical waste which is difficult to treat and the purity issues makes the crystalline Raltegravir potassium Form 3 not suitable for pharmaceutical formulations and therapeutic use thereof. Moreover, the inventors have now found that crystalline Raltegravir potassium Form 3 obtained by the methods described in above references is very unstable and has tendency to converts in to Form 1.
A need still remains for simple, cost effective, consistently reproducible and environmental friendly processes for preparing highly pure and stable crystalline Raltegravir potassium Form 3 which is free from other polymorphs.